Premature infants of gestational age (GA) > 34 weeks are usually able to coordinate sucking, swallowing, and breathing, and so establish breast or bottle feeding. In less mature infants, oral feeding may not be safe or possible because of neurological immaturity or respiratory compromise [20]. In these infants, milk can be given as a continuous infusion or as an intermittent bolus through a fine feeding catheter passed via the nose or the mouth to the stomach [22]. In older babies, around 34 weeks of GA, the infant begins to suckle, and the bottle progressively replaces the tube feeding.

Several Cochrane reviews [23–26] confirm that the introduction of enteral feeding for very preterm infants, that is, less than 32 weeks of GA or very low birth weight (VLBW) < 1500 g infants, is often delayed due to the bad clinical tolerance of early enteral introduction and may increase the risk of developing NEC. However, the available trial data suggest that introducing progressive enteral feeding before 4 days after birth and advancing the rate of feed quantities at more than 24 ml/kg/day do not increase the risk of NEC in very preterm infants and VLBW infants [23–26]. In contrast, prolonged enteral fasting may diminish the functional adaptation of the immature GI tract and extend the need for parenteral nutrition with its attendant infectious and metabolic risks [26]. Also, delayed introduction or slow advancement of enteral feeding results in several days of delay in the time taken to regain birth weight and establish full enteral feeds [26]. Trophic feeding, giving preterm infants very small quantities of adapted preterm milk formulas to promote intestinal maturation, may enhance feeding tolerance and decrease the time taken to reach full enteral feeding independently of parenteral nutrition [23–26]. Although it is well agreed that oral feeding should be initiated slowly first by the help of nasogastric tube and then progressively followed by oral feeding, the way in which the preterm infants are introduced and advanced varies widely. The use of dilute formula in preterm or VLBW infants might leads to an important reduction in the time taken for those infants to achieve an adequate daily energy intake [27]. Uncertainty also exists about the risk–benefit balance of different enteral feeding strategies in human milk-fed versus formula-fed very preterm or VLBW infants as the trials and reviews did not contain sufficient data for subgroup analyses [26].

NEC is a devastating GI disease dominating in preterm infants . The pathogenesis, likely multifactorial, is incompletely understood. At this age, infants experience multiple perturbations to normal postnatal intestinal and immune development, all of which increase their vulnerability to NEC. The prevalence is increased in formula-fed infants, suggesting protection by the bioactive compounds of breast milk. The intestinal microbiota profiles observed during NEC as compared to control infants, suggests a lack of benefits from commensal bacteria and an increased risk of intestinal inflammation and bacterial translocation by pathogenic bacteria [31]. NEC incidence also seems reduced by prebiotics and probiotics and increased after prolonged antibiotics exposure use leading to delayed bacterial colonization, with preference for pathogenic microorganisms. H2-blocker or PPI, decreasing gastric acidity, might dampen one component of the first-line defense against pathogenic antigens provided by intestinal tract [32].

The role of Toll-like receptor-4 (TLR4) is likely to be critical in the postnatal susceptibility to NEC of preterm infants [33]. In animal models, the absence of TLR4, such as in TLR4 knockout mouse, prevented the development of NEC [34]. Downregulation of TLR4 suppresses downstream pro-inflammatory signaling, such as observed with postnatal intestinal bacterial colonization by commensal organisms, whereas TLR4 activation increases pro-inflammatory signaling. TLR4 activation might also mediate other downstream pathways and reduce the epithelial cells capacity for regeneration and proliferation [35] .

NEC affects typically premature infants , with a timing of onset generally inversely proportional to the GA of the child. Initial symptoms include feeding intolerance, increased gastric residuals, abdominal distension, and bloody stools. Symptoms may progress rapidly to abdominal discoloration with intestinal perforation and peritonitis and systemic hypotension requiring intensive medical support [36] .

The diagnosis is usually suspected clinically but often requires the aid of diagnostic imaging modalities. Radiographic signs of NEC include dilated bowel loops, paucity of gas, a “fixed loop” (unaltered gas-filled loop of bowel), pneumatosis intestinalis, portal venous gas, and pneumoperitoneum (extra-luminal or “free air” outside the bowel within the abdomen). More recently, ultrasonography has proven to be useful as it may detect signs and complications of NEC before they are evident on radiographs [37]. Recently, fecal biomarkers, such as fecal calprotectin, have been tested as noninvasive markers for diagnosis and follow-up [38, 39].

Three stages exist:

Primary treatment consists of supportive care. Bowel rest is obtained by stopping enteral feeds, intermittent suction to obtain gastric decompression , fluid repletion to correct electrolyte abnormalities and third space losses, adapted support for blood pressure, parenteral nutrition , and prompt antibiotic therapy . Monitoring is clinical, although serial supine and left lateral decubitus abdominal roentgenograms should be performed every 6 h. Where the disease is not halted through medical treatment alone, or when the bowel perforates, immediate emergency surgery to remove the dead bowel is generally required. Surgery may require a colostomy, which may be able to be reversed at a later time. Some children may suffer later as a result of short bowel syndrome (SBS) if extensive portions of the bowel had to be removed.

The American Academy of Pediatrics, in a 2012 policy statement, recommended feeding preterm infants human milk, finding “significant short- and long-term beneficial effects,” including lower rates of NEC. Meta-analyses of four randomized clinical trials performed over the period 1983–2005 support the conclusion that feeding preterm infants human milk is associated with a significant reduction (58 %) in the incidence of NEC. A more recent study of preterm infants fed an exclusive human milk diet compared with those fed human milk supplemented with cow-milk-based infant formula products noted a 77 % reduction in NEC [40] .

A study demonstrated that using a higher rate of lipid (fats and/or oils), infusion for preterm or VLBW infants in the first week of life resulted in zero infants developing NEC in the experimental group, compared with 14 % with NEC in the control group [41].

Neonatologists from NICU reported on the importance of providing small amounts of trophic oral feeds of human milk starting, while the infant is being primarily fed intravenously, to prime the immature gut to mature and become ready to receive greater oral intake [40]. Human milk from a milk bank or donor can be used if mother’s milk is unavailable [40]. Finally, probiotic and prebiotic supplementation is a promising approach for the prevention of NEC in preterm and VLBW infants [42].

Typical recovery from NEC if medical, nonsurgical treatment succeeds includes 10–14 days or more without oral intake and then demonstrated ability to resume feedings and gain weight. Recovery from NEC alone may be compromised by comorbid conditions that frequently accompany prematurity. Long-term complications of medical NEC include bowel obstruction, anemia, and SBS .

MI results from an intra-luminal intestinal obstruction produced by thick inspissated meconium. Most patients have cystic fibrosis (CF) disease (90 % of cases), others having a history of isolated simple MI. The abnormal meconium is very dry, contains higher-than-usual concentrations of protein, and adheres firmly to the mucosal surface of the distal small bowel, creating an intra-luminal obstruction [43]. This leads to poor intestinal motility, low-grade obstruction, distended loops without air fluid levels. Associated risk factors are severe prematurity and low birth weight, caesarean delivery, maternal MgSO₄ therapy, and maternal diabetes. The incidence of MI has shown to increase while its management continues to be challenging and controversial for the risk of complicated obstruction and perforation [44].

MI is usually manifested by intestinal obstruction. This situation is more common in the very preterm and VLBW infants than preterm infants more than 32-week GA. Clinically, in an otherwise healthy-appearing infant, abdominal distension is visible in the first 12–24 h of life, without meconium elimination in the first 48 h. Physical examination reveals firm palpable masses throughout the abdomen without real surgical signs. There may be feeding difficulties with increased gastric residuals but without vomiting.

MI may be complicated in utero by volvulus, atresia, perforation, and meconium peritonitis, in 30–50 % of the cases. When infants born with those complications, infants appear sicker, with often vomiting and signs of neonatal sepsis and more marked abdominal distension causing respiratory distress.

Radiological examination shows dilated bowel loops, and the viscous nature of meconium produces a “ground-glass” appearance. Perforation after birth results in free intraperitoneal air. Newborns suspected of MI or any other distal bowel obstruction are diagnosed with a contrast enema study.

All newborns with MI need to be assessed for CF with the sweat chloride test and the genetic assessment of the several mutations of Cystic fibrosis transmembrane conductance regulator gene (CFTR gene) [43] .

In case of simple MI, approximately 60 % of infants have their obstruction successfully relieved by diagnostic contrast enema, ideally using a water-soluble contrast agent [43]. Failure of the contrast to dislodge the inspissated meconium after two attempts is an indication for surgical intervention and for enterotomy with acetylcysteine irrigation and immediate closure. When the enema fails, acetylcysteine, 5 ml every 6 h, may be given via a nasogastric tube to help complete the clean-out. Complicated MI always requires surgical interventions, and the choice of operations depends on the pathologic findings [43].

Esophageal atresia (EA) is a congenital anomaly of the tracheoesophageal separation where the development of the midst esophagus is lacking and that occurs either rarely isolated or frequently associated with tracheoesophageal fistula (TEF). In the most frequent case (85 %), the TEF is located in the distal esophagus (see Table 5.5).